A clinical audit of patient outcomes in real-world acupuncture practice.

INTRODUCTION: Clinical auditing represents a valuable and cost-effective method for the collection of patient outcomes and is increasingly being used to inform clinical guidelines. The aim of this clinical audit was to assess patient outcomes across a small subset of acupuncture practitioners and private practices in the United Kingdom. METHODS: The Measure Yourself Medical Outcomes Profile (MYMOP) questionnaire and the Patient Global Impression of Change (PGIC) scale were used as outcome measures. Additional questions assessed adverse events and patient experience with care. Clinical data were collected utilising an electronic patient-reported outcome measures (ePROMs) system. RESULTS: Baseline data were collected for a total of 233 health complaints (from 232 patients), of which 45.9% were musculoskeletal and 26.2% were psychological. Follow-up outcomes data were available for 144 health complaints (61.8% completion rate). For PGIC responses, >90% of health complaints were reported as at least 'minimally improved'. This was reduced to >51% when controlling for missing data. There was a gradual improvement in both mean MYMOP scores (24.5%-43.0%) and PGIC responses of 'very much improved' (12.3%-56.3%) over a 6-month period. A clinically significant improvement (>1 point change, p ⩽ 0.001) was seen in mean MYMOP scores compared to baseline from 4 to 8 weeks and symptom 1 MYMOP scores from 1 to 4 weeks. A moderately strong, negative correlation was seen between outcome measures (r = -0.507, p < 0.001). CONCLUSIONS: The majority of patients reported clinically meaningful improvements for their main health complaints/symptoms, which appeared to be sustained in the medium to long-term.

A clinical audit in a UK-based acupuncture private practice: assessing patient demographics, outcomes and experience.

OBJECTIVES: The aim of this clinical audit was to assess patient demographics, outcomes and experience with care in patients who received acupuncture in a private practice setting in the United Kingdom. METHODS: Demographic and clinical data were extracted from patients' records over a 7-year period. The Measure Yourself Medical Outcomes Profile (MYMOP) questionnaire and an adapted Patient Global Impression of Change (PGIC) scale were used routinely to monitor patient outcomes over an 18-month period. Finally, a retrospective questionnaire was used to assess patient beliefs regarding treatment effectiveness, adverse events and overall experience with care. Patients not providing consent or known to be deceased were excluded. RESULTS: Data were collected for 306 patients presenting with 376 separate health complaints, 58% of which were musculoskeletal. Follow-up outcomes (MYMOP scores (n = 51) and PGIC scale responses (n = 50)) showed a clinically significant improvement compared to baseline for the majority of health complaints (93% of PGIC scores were 'improved' and 79% MYMOP demonstrated > 1 point change). Total mean MYMOP severity scores were reduced by almost 50% (p < 0.001) after 1-4 weeks, and this was sustained in the medium-to-long term. There was a strong negative correlation (r = -0.767, p < 0.001) between the MYMOP and PGIC scores. A total of 118 health complaints were reported by 85/255 patients who responded to a retrospective questionnaire. Over 84% of patients believed that the treatments they received were 'effective' at addressing their health complaints. Seven minor adverse events were reported and four patients experienced negative treatment outcomes. CONCLUSIONS: Although musculoskeletal conditions were the most common, this audit found that patients sought treatment for a wide range of predominantly chronic health complaints, for many of which there is a currently a lack of quality evidence to support the use of acupuncture. Overall, the small sample of patients who responded to outcome questionnaires reported clinically meaningful and sustained improvements.

The Patient Journey in Facial Aesthetics: Findings from a European Consensus Meeting on Improving the Quality of Life for Patients Receiving Botulinum Toxin Injections.

Purpose: Successful treatment of facial lines with botulinum toxin is largely dependent on patient satisfaction; thus, a structured treatment journey that uses patient-reported outcomes (PROs) is helpful for maximizing botulinum toxin results. To develop a patient-centric approach for botulinum toxin injections in facial aesthetics, a group of clinicians met to provide opinions on an optimal treatment journey that uses PROs to quantify treatment benefits on patient quality of life. Patients and Methods: A multidisciplinary panel of 9 clinicians with expertise in facial aesthetic procedures convened for an advisory board that was preceded by and followed up with a structured, multistep consensus discussion. Based on current literature, the panel's expertise, structured questions, and group discussion, panelists assessed, reconciled, and agreed upon on a patient journey for botulinum toxin treatment in facial aesthetics. Results: Panelists agreed that an optimal patient journey includes screening, assessment, treatment, posttreatment, and follow-up visits. A compact, easy-to-complete, and digital PRO questionnaire should be provided before the visit. During screening, thorough assessments are integral for a successful patient journey because they provide an opportunity to understand treatment goals, address patient concerns, discuss risks and benefits, obtain medication lists/medical history, and take pretreatment photographs. Treatment strategies should include discussing and educating on the approach/choice of botulinum toxin and ensuring patients are comfortable. Posttreatment, clinicians should request intense muscle movements to enhance product uptake and be available to address patient concerns. Finally, during follow-up, PRO questionnaires can be provided to gauge patient satisfaction with treatment, and pretreatment photographs can be provided to allow patients to track their progression. Follow-ups should be scheduled with new patients or those reporting low satisfaction. Conclusion: Establishing a relationship, being aware of the patient's goals, and developing an individualized care plan allows for a structured, patient-centered treatment journey that promotes positive aesthetic outcomes.

An alternative mode of epithelial polarity in the Drosophila midgut.

Apical-basal polarity is essential for the formation and function of epithelial tissues, whereas loss of polarity is a hallmark of tumours. Studies in Drosophila have identified conserved polarity factors that define the apical (Crumbs, Stardust, Par-6, atypical protein kinase C [aPKC]), junctional (Bazooka [Baz]/Par-3), and basolateral (Scribbled [Scrib], Discs large [Dlg], Lethal [2] giant larvae [Lgl]) domains of epithelial cells. Because these conserved factors mark equivalent domains in diverse types of vertebrate and invertebrate epithelia, it is generally assumed that this system underlies polarity in all epithelia. Here, we show that this is not the case, as none of these canonical factors are required for the polarisation of the endodermal epithelium of the Drosophila adult midgut. Furthermore, like vertebrate epithelia but not other Drosophila epithelia, the midgut epithelium forms occluding junctions above adherens junctions (AJs) and requires the integrin adhesion complex for polarity. Thus, Drosophila contains two types of epithelia that polarise by fundamentally different mechanisms. This diversity of epithelial types may reflect their different developmental origins, junctional arrangement, or whether they polarise in an apical-basal direction or vice versa. Since knock-outs of canonical polarity factors in vertebrates often have little or no effect on epithelial polarity and the Drosophila midgut shares several common features with vertebrate epithelia, this diversity of polarity mechanisms is likely to be conserved in other animals.

Analysis of the expression patterns, subcellular localisations and interaction partners of Drosophila proteins using a pigP protein trap library.

Although we now have a wealth of information on the transcription patterns of all the genes in the Drosophila genome, much less is known about the properties of the encoded proteins. To provide information on the expression patterns and subcellular localisations of many proteins in parallel, we have performed a large-scale protein trap screen using a hybrid piggyBac vector carrying an artificial exon encoding yellow fluorescent protein (YFP) and protein affinity tags. From screening 41 million embryos, we recovered 616 verified independent YFP-positive lines representing protein traps in 374 genes, two-thirds of which had not been tagged in previous P element protein trap screens. Over 20 different research groups then characterized the expression patterns of the tagged proteins in a variety of tissues and at several developmental stages. In parallel, we purified many of the tagged proteins from embryos using the affinity tags and identified co-purifying proteins by mass spectrometry. The fly stocks are publicly available through the Kyoto Drosophila Genetics Resource Center. All our data are available via an open access database (Flannotator), which provides comprehensive information on the expression patterns, subcellular localisations and in vivo interaction partners of the trapped proteins. Our resource substantially increases the number of available protein traps in Drosophila and identifies new markers for cellular organelles and structures.

Slmb antagonises the aPKC/Par-6 complex to control oocyte and epithelial polarity.

The Drosophila anterior-posterior axis is specified when the posterior follicle cells signal to polarise the oocyte, leading to the anterior/lateral localisation of the Par-6/aPKC complex and the posterior recruitment of Par-1, which induces a microtubule reorganisation that localises bicoid and oskar mRNAs. Here we show that oocyte polarity requires Slmb, the substrate specificity subunit of the SCF E3 ubiquitin ligase that targets proteins for degradation. The Par-6/aPKC complex is ectopically localised to the posterior of slmb mutant oocytes, and Par-1 and oskar mRNA are mislocalised. Slmb appears to play a related role in epithelial follicle cells, as large slmb mutant clones disrupt epithelial organisation, whereas small clones show an expansion of the apical domain, with increased accumulation of apical polarity factors at the apical cortex. The levels of aPKC and Par-6 are significantly increased in slmb mutants, whereas Baz is slightly reduced. Thus, Slmb may induce the polarisation of the anterior-posterior axis of the oocyte by targeting the Par-6/aPKC complex for degradation at the oocyte posterior. Consistent with this, overexpression of the aPKC antagonist Lgl strongly rescues the polarity defects of slmb mutant germline clones. The role of Slmb in oocyte polarity raises an intriguing parallel with C. elegans axis formation, in which PAR-2 excludes the anterior PAR complex from the posterior cortex to induce polarity, but its function can be substituted by overexpressing Lgl.

In vivo analysis of proteomes and interactomes using Parallel Affinity Capture (iPAC) coupled to mass spectrometry.

Affinity purification coupled to mass spectrometry provides a reliable method for identifying proteins and their binding partners. In this study we have used Drosophila melanogaster proteins triple tagged with Flag, Strep II, and Yellow fluorescent protein in vivo within affinity pull-down experiments and isolated these proteins in their native complexes from embryos. We describe a pipeline for determining interactomes by Parallel Affinity Capture (iPAC) and show its use by identifying partners of several protein baits with a range of sizes and subcellular locations. This purification protocol employs the different tags in parallel and involves detailed comparison of resulting mass spectrometry data sets, ensuring the interaction lists achieved are of high confidence. We show that this approach identifies known interactors of bait proteins as well as novel interaction partners by comparing data achieved with published interaction data sets. The high confidence in vivo protein data sets presented here add new data to the currently incomplete D. melanogaster interactome. Additionally we report contaminant proteins that are persistent with affinity purifications irrespective of the tagged bait.

Twisted gastrulation limits apoptosis in the distal region of the mandibular arch in mice.

The mandibular arch (BA1) is critical for craniofacial development. The distal region of BA1, which gives rise to most of the mandible, is dependent upon an optimal level of bone morphogenetic protein (BMP) signaling. BMP activity is modulated in the extracellular space by BMP-binding proteins such as Twisted gastrulation (TWSG1). Twsg1(-/-) mice have a spectrum of craniofacial phenotypes, including mandibular defects that range from micrognathia to agnathia. At E9.5, the distal region of the mutant BA1 was prematurely and variably fused with loss of distal markers eHand and Msx1. Expression of proximal markers Fgf8 and Barx1 was expanded across the fused BA1. The expression of Bmp4 and Msx2 was preserved in the distal region, but shifted ventrally. While wild type embryos showed a gradient of BMP signaling with higher activity in the distal region of BA1, this gradient was disrupted and shifted ventrally in the mutants. Thus, loss of TWSG1 results in disruption of the BMP4 gradient at the level of signaling activity as well as mRNA expression. Altered distribution of BMP signaling leads to a shift in gene expression and increase in apoptosis. The extent of apoptosis may account for the variable degree of mandibular defects in Twsg1 mutants.

Optimizing poly-L-lactic acid use.

Injectable devices are less invasive than surgical interventions for restoring youthful contours. Sculptra (Dermik Laboratories, Bridgewater, NJ, USA, a business of sanofi aventis U.S. LLC) contains poly-l-lactic acid (PLLA), which is thought to elicit in vivo collagen production around the injected implant, producing new volume gradually over time, and with effects lasting up to 2 years. Correct reconstitution and preparation of PLLA, as well as injection technique, are essential to ensure optimal outcomes and reduce adverse events. This article provides an overview of injectable devices, specifically focusing on PLLA in cosmetic application and optimal administration techniques to maximize efficacy and duration of effect.

An oskar-dependent positive feedback loop maintains the polarity of the Drosophila oocyte.

The localization of oskar mRNA to the posterior of the Drosophila oocyte defines the site of assembly of the pole plasm, which contains the abdominal and germline determinants. oskar mRNA localization requires the polarization of the microtubule cytoskeleton, which depends on the recruitment of PAR-1 to the posterior cortex in response to a signal from the follicle cells, where it induces an enrichment of microtubule plus ends. Here, we show that overexpressed oskar mRNA localizes to the middle of the oocyte, as well as the posterior. This ectopic localization depends on the premature translation of Oskar protein, which recruits PAR-1 and microtubule-plus-end markers to the oocyte center instead of the posterior pole, indicating that Oskar regulates the polarity of the cytoskeleton. Oskar also plays a role in the normal polarization of the oocyte; mutants that disrupt oskar mRNA localization or translation strongly reduce the posterior recruitment of microtubule plus ends. Thus, oskar mRNA localization is required to stabilize and amplify microtubule polarity, generating a positive feedback loop in which Oskar recruits PAR-1 to the posterior to increase the microtubule cytoskeleton's polarization, which in turn directs the localization of more oskar mRNA.

A new technique for rendering complex portals.

In this paper, we identify a general paradigm for portal-based rendering and present an image-space algorithm for rendering complex portals. Our general paradigm is an abstraction of portal-based rendering that is independent of scene geometry. It provides a framework for flexible and dynamic scene composition by connecting cells with transformative portals. Our rendering algorithm maintains a visible volume in image-space and uses fragment culling to discard fragments outside of this volume. We discuss our implementation in OpenGL and present results that show it provides correct rendering of complex portals at interactive rates on current hardware. We believe that our work will be useful in many applications that require a means of creating dynamic and meaningful visual connections between different sets of data.

Identification of novel protein-protein interactions using a versatile mammalian tandem affinity purification expression system.

Identification of protein-protein interactions is essential for elucidating the biochemical mechanism of signal transduction. Purification and identification of individual proteins in mammalian cells have been difficult, however, due to the sheer complexity of protein mixtures obtained from cellular extracts. Recently, a tandem affinity purification (TAP) method has been developed as a tool that allows rapid purification of native protein complexes expressed at their natural level in engineered yeast cells. To adapt this method to mammalian cells, we have created a TAP tag retroviral expression vector to allow stable expression of the TAP-tagged protein at close to physiological levels. To demonstrate the utility of this vector, we have fused a TAP tag, consisting of a protein A tag, a cleavage site for the tobacco etch virus (TEV) protease, and the FLAG epitope, to the N terminus of human SMAD3 and SMAD4. We have stably expressed these proteins in mammalian cells at desirable levels by retroviral gene transfer and purified native SMAD3 protein complexes from cell lysates. The combination of two different affinity tags greatly reduced the number of nonspecific proteins in the mixture. We have identified HSP70 as a specific interacting protein of SMAD3. We demonstrated that SMAD3, but not SMAD1, binds HSP70 in vivo, validating the TAP purification approach. This method is applicable to virtually any protein and provides an efficient way to purify unknown proteins to homogeneity from the complex mixtures found in mammalian cell lysates in preparation for identification by mass spectrometry.

Repeat courses of intravenous alefacept in patients with chronic plaque psoriasis provide consistent safety and efficacy.

BACKGROUND: Psoriasis is a chronic, relapsing skin disease that may require multiple treatment courses. Alefacept targets the memory T cells implicated in psoriasis pathogenesis. This open-label study evaluated the safety and tolerability, efficacy, and pharmacodynamics of repeat courses of alefacept in men and women with chronic plaque psoriasis. This article reports the interim results of this ongoing study. METHODS: Patients (n = 174) who participated in previous phase II studies of alefacept were included in this retreatment study. Intravenous alefacept (7.5 mg) was administered once weekly for 12 weeks followed by 12 weeks of observation. Initial and subsequent retreatment courses were only given when, in the opinion of the investigators, disease had returned and necessitated treatment; CD4+ T-cell counts had to be at or above the lower limit of normal. RESULTS: Adverse events were similar regardless of the retreatment course. No opportunistic infections, rebound of disease, or flares were reported. Low titers of anti-alefacept antibodies occurred in a few patients without related safety issues. Sixty-six per cent of patients achieved a >/= 50% reduction in the Psoriasis Area and Severity Index (PASI) at any time after the first dose of retreatment course 1. Patients who received two retreatment courses (n = 50) had consistent or improved responses after the second course; 64% and 68% of these patients achieved a >/= 50% PASI improvement at any time after the first dose of retreatment courses 1 and 2, respectively. Alefacept selectively reduced memory T cells without cumulative effects. CONCLUSIONS: Repeat courses of alefacept were well tolerated, and subsequent retreatment courses were at least as effective as the initial course of therapy.